Studies in patients with Alzheimer's disease (AD) using positron emission tomography (PET) show impaired brain glucose utilization in brain association regions. Postmortem brains from AD patients showed 40% to 60% decreases in levels of mRNA coding for subunits of oxidative-phosphorylation (OXPHOS) complexes within mitochondria, for mitochondrial DNA (mtDNA) encoded - cytochrome oxidase (COX) subunits I, III and NADH-dehydrogenase subunit 1 as well as for nuclear DNA (nDNA) encoded COX subunit IV and ATPase-beta in midtemporal association cortex but not primary motor cortex, compared with control regions. There was no difference in expression of the mitochondrial 12S rRNA (mitochondrial transcript) gene, nuclear lactate dehydrogenase subunit B (a marker of glycolytic metabolism) gene, or nuclear beta actin gene. COX enzyme activity was decreased by 34% in temporal association neocortex of AD brains compared with control cortex. Neuron specific expression of ND4, a mtDNA-encoded subunit of NADH dehydrogenase was decreased. Results suggest physiological down-regulation of OXPHOS gene expression. Cytochrome oxidase inhibition in the rat, induced by continuous infusion of sodium azide, when combined with low dose corticosterone, resulted in neuronal death in striatum.